Pseudomonas aeruginosa is a prevalent opportunistic bacterial pathogen in humans and animals. P. aeruginosa is the most common Gram-negative bacterium found in nosocomial infections, especially in immunocompromised individuals. It is frequently related to ventilator-associated pneumonia in intubated patients. Pseudomonas infection is common amongst patients with cystic fibrosis, burn wounds, organ transplants, and intravenous-drug addiction. Cystic fibrosis patients are often chronically infected by P. aeruginosa, which is responsible for increased illness and death in this particular population. P. aeruginosa bacteremia is responsible for high death rates in burn units. Pseudomonas can lead to serious conditions such as endophthalmitis, endocarditis, meningitis, pneumonia, and septicaemia. Septicemia due to P. aeruginosa is associated with the highest death rates of all Gram-negative infections.
Since P. aeruginosa is naturally resistant to many antibiotics, there is a need for the development of a vaccine that will protect individuals from P. aeruginosa infection. An infection by P. aeruginosa induces an immune response against antigens found at the surface of the bacterial cells. However, many of these surface proteins are still not characterized, nor has the immune response resulting in protection from infection by different strains been determined.
To develop a vaccine that will protect individuals from. P. aeruginosa infection, efforts have mainly been concentrated on lipopolysaccharides (LPS). However, even though a limited number of LPS serotypes are associated with clinical cases, the production of a multivalent LPS-based vaccine is complex and may induce serotype replacement in vaccinated individuals. Anti-flagellar and anti-pili vaccines are also evaluated but the regulation of flagella/pili expression at different P. aeruginosa infection stages may prevent effective protection. Outer membrane proteins (OMP) are also being tested. An OMP preparation from 4 different P. aeruginosa serotypes is currently in clinical trials but the specificity of the protection confered by this preparation remains to be evaluated. A recombinant fusion protein, based on outer membrane proteins OprF and OprI, is considered a promising vaccine candidate. However, the OprF protein was shown to be absent from some clinical strains of P. aeruginosa and the protection confered by the OprI protein alone has not been evaluated yet.
A review of existing technology is described in Stanislavsky E S and Lam J S. (1997) FEMS Microbiol. Rev. 21(3): 243-77 and Holder I A. (2001) J. Burn Care Rehabil. 22(5): 311-20.
The sequence of the genome of P. aeruginosa strain PAO1 was determined in a collaboration among the Cystic Fibrosis Foundation, the University of Washington and Pathogenesis Corporation and is available at the Internet site (http://www): pseudomonas.com/, the Internet site (http://www): tigr.org/tigr-scripts/CMR2/Genome Page3.spl?database=n tpa03, the Internet site (http://) pseudomonas.bit.uq.edu.au/ and in Nature, Stover et al. 406:959-964 (2000).
Therefore there remains an unmet need for P. aeruginosa polypeptides that may be used to prevent, diagnose and/or treat P. aeruginosa infection.